Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.
In the developing mammalian nervous system, neural progenitor cells first express the Notch effector Hes1 at variable levels and then proneural genes and Notch ligands in salt-and-pepper patterns. Recent real-time imaging analysis indicates that Hes1 expression in these cells oscillates with a period of about 2-3 h. Furthermore, the proneural gene Neurogenin-2 (Ngn2) and the Notch ligand gene Deltalike-1 (Dll1) are expressed cyclically in neural progenitor cells under the control of Hes1 oscillation but are expressed continuously in postmitotic neurons, which lose Hes1 expression. Hes1-driven Ngn2 and Dll1 oscillations seem to be advantageous for maintenance of a group of cells in an undifferentiated state by mutual activation of Notch signaling. This dynamic mode of gene expression would require a revision of the traditional view of how Notch-mediated lateral inhibition operates in the developing mammalian nervous system.
Kageyama
Ryoichiro
R
Institute for Virus Research, Kyoto University and Japan Science and Technology Agency, CREST, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.
Ohtsuka
Toshiyuki
T
Shimojo
Hiromi
H
Imayoshi
Itaru
I
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D008954:Models, Biological; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D017711:Nonlinear Dynamics; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
D051880:Receptors, Notch